Continuous renal replacement therapy is currently used as a standard treatment for acute kidney injury in the intensive care unit, particularly for patients with unstable hemodynamic status. Because this therapy is continuous, for days or weeks, and the extracorporeal blood circuit is large, the circuit is prone to clotting. Several methods of keeping the extracorporeal circuit patent are available, including heparin infusion, flushes with physiological saline, use of thrombin inhibitors, and citrate. This article reviews methods for continuous renal replacement therapy, anticoagulation, efficacy, and implications for bedside critical care. (Critical Care Nurse. 2016;36[2]:34-42)